Pyrroline production



ware

No Drawing. Filed Aug. 7, 1964, Ser. No. 388,300

7 Claims. (Cl. 260-3131) This invention relates to an improved method for the production of certain heterocyclic compounds. More particularly, it relates to an improved method for the production of pyrrolines.

Few methods are available for the production of pyrrolines. Probably the most frequently employed method comprises chemical reduction of the corresponding pyrrole, as with active metal and acid. Such a method suffers from the disadvantage that the pyrrole reactant, particularly if a substituted pyrrole, may be difiicult to prepare and/ or economically expensive. It would be of advantage to provide a method whereby pyrrolines are easily and economically produced.

It is the object of the present invention to provide an improved process for the production of certain nitrogencontaining heterocyclic compounds. A more particular object is to provide an improved process for the production of pyrrolines.

It has now been found that these objects are accomplished by reacting hydrocarbon aziridines with acetylenic compounds at elevated temperature, Under the reaction conditions of the process, pyrrolines, frequently together with lesser amounts of the corresponding pyrroles, are produced easily and efficiently and in good yield by a onestep addition process.

The aziridine reactants of the process of the invention, which are also commonly referred to as enimines, contain a three-membered heterocyclic ring comprising one atom of nitrogen and two atoms of carbon. Suitable aziridines are hydrocarbon aziridines, that is, contain only atoms of carbon and hydrogen besides the nitrogen moiety of the :three-membered ring and are free from non-aromatic unsaturation. Illustrative compounds of this type contain from 2 to 10 carbon atoms, preferably 2 to 6, and are represented by the formula wherein R and R independently are hydrogen, alkyl of up to 8 carbon atoms, aralkyl of up to 8 carbon atoms, phenyl, or alkarylv having from 6 to 8 carbon atoms.

Illustrative of such compounds are ethylenimine, N-methylethylenimine, 1,2-dimethylaziridine, 1,2,3-triethylaziridine, 2,2-dimethylaziridine, N-butylethylenimine, N-phenylethylenimine, 2-tolylaziridine, N-benzylethylenimine, N-amylethylenimine and 2-octylaziridine. Preferred aziridines of the above-depicted formula are Wholely aliphatic, that is, contain no aromatic moieties. Further preferred are those above-depicted aziridines wherein all R substituents are hydrogen, i.e., a l-(nonto mono-)alkylaziridine wherein any l-alkyl substituent has from 1 to 8 carbon atoms, preferably 1 to 4. From consideration of economics and of product utility, most preferred as the aziridine reactant is ethylenimine.

In the process of the invention, the aziridine is reacted with an acetylenic compound, i.e., a compound containing a carbon-carbon triple bond. Although acetylenic compounds of varying type, e.g., hydrocarbon acetylenes and non-hydrocarbon acetylenes, are operable provided that any non-hydrocarbyl substituents do not possess active hydrogens, the non-hydrocarbon acetylenes are United States Patent "ice generally difficult to obtain and/or economically expensive, and largely for these reasons the utilization of hydrocarbon acetylenes is preferred. The preferred acetylenic compounds therefore contain only atoms of carbon and hydrogen and preferably contain only a single carboncarbon triple bond as the only non-aromatic unsaturation in the molecule. Suitable acetylenic compounds contain from 2 to 10 carbon atoms, preferably from 2 to 8, and are represented by the formula wherein R has the previously stated significance. Exemplary acetylenic compounds include acetylene, propyne, l-butyne, Z-butyne, l-hexyne, 2-octyne, 3-octyne, phenylacetylene, 3-phenylpropyne and the like. In general, regardless of the number of carbon atoms present, terminal acetylenes are preferred over the corresponding internal acetylenes, and particularly preferred as the acetylenic reactant is acetylene.

Without Wishing to be bound by any specific theory, it appears that the process of the invention involves thermal cleavage of a carbon-nitrogen bond of the aziridine ring to form a 1,3-diradical and subsequent 1,3-cycloaddition of the diradical to the multiple linkage of the acetylenic reactant to form a five-membered, nitrogen-containing ring. In view of the known highly reactive character of the free radicals as well as the acetylenic compounds at the elevated temperature of the reaction, it is surprising that high selectivity towards the 1,3-cycloaddition process is observed. The reaction is conducted at temperatures above that which is required for aziridine ring cleavage, but below temperatures at which extensive polymerization or decomposition of the reacting species or product is observed. Suitable temperatures vary from about 250 C. to about 500 C., although temperatures from about 300 C. to about 450 C. are preferred.

The efficiency of the pyrroline production is favored by an excess of the acetylenic compound over the aziridine whereby the likelihood of the acetylene trapping of the diradical produced by aziridine ring cleavage is increased. Thus, a molar excess of the acetylenic reactant is preferably employed. From practical considerations, however, utilization of too great an excess of acetylenic compound renders process operation and product recovery more difficult due to the bulk of the product mixture. Molar ratios of acetylenic compound to aziridine from about 1.5 :1 to about :1 are generally satisfactory, while molar ratios from about 2:1 to about 25:1 are preferred.

The reaction process is desirably conducted in a manner whereby the contact time of the reactants can be controlled, as undesirable side reactions may occur at extended reactant contact times. Thus, although batch type processes are not precluded, best results are obtained when the process is conducted in a continuous manner. A preferred modification of a continuous process comprises conducting the reaction in the vapor phase, as by passing a gaseous mixture of the acetylenic compound and the aziridine through a reactor maintained at the desired reaction temperature. The reactants may be mixed prior to or simultaneously with introduction into the reactor which is customarily tubular in shape. In the case of higher molecular weight acetylenes which are normally liquid at ambient temperature it is preferred to employ preheating means to promote extensive vaporization of the acetylene prior to mixing with the aziridine or introduction into the reactor, and it is also useful to pack the reactor with an inert material, e.g., glass helices, to promote more even heat transfer. Customarily the excess of acetylene or alternatively an inert gas such as nitrogen, helium, methane or other unreactive hydrocarbon, argon or the like is employed as a transport agent to facilitate passage of the gaseous reactants through the reactor. The reaction is conducted at atmospheric, subatmospheric or superatmospheric pressure, so long as the reactants remain in the vapor phase. The pressure at which the gaseous materials are introduced to the reactor will in part determine the reactant residence time, and at the substantially atmospheric reaction pressures preferably employed, e.g., from about 0.5 atmosphere to about 2 atmospheres, residence times of up to about minutes are encountered. Preferred reactant residence times vary from about 0.5 minute to about 7 minutes.

Subsequent to reaction the effluent from the reactor is separated and recovered by conventional means, e.g., by fractional distillation, selective extraction, crystallization or the like after cooling the efiluent to condense the product mixture. The unreacted acetylenic compound is recoverable for further reaction.

The heterocyclic product of the processes comprises the pyrroline product, generally with lesser amounts of the corresponding pyrrole. Without wishing to be bound by any specific theory, it appears that the aziridine and acetylenic compound react to initially produce a A -pyrroline, which product gains stability by isomerization to the corresponding A -pyrroline or by elimination of hydrogen to produce the corresponding pyrrole. In any event, the principal products typically observed comprise a mixture of a A -pyrroline and the corresponding pyrrole. The illustrative reaction of ethylenimine and propyne is shown by the equation below.

When the aziridine possesses substituents or when other acetylenes are employed, the pyrroline and any pyrrole products contain corresponding substituents upon the fivemembered ring. For example, from N-methylaziridine and l-hexyne is obtained 1 methyl-3-butyl A pyrroline. When the preferred terminal acetylenes are employed, the group attached to the carbon-carbon triple bond is observed as a 3-substituent upon the heterocyclic product, and such products constitute a preferred class. Other illustrative pyrroline products include l-ethyl-A -pyrroline, 2,3-dimethyl-A -pyrroline, 3-benzyl-A -pyrroline, 1-phenyl-3-hexyl-A -pyrroline and 2,4-dimethyl-A -pyrroline.

The pyrroline products find utility as solvents and as chemical intermediates, particularly in the production of agricultural chemicals, e.g., insecticides, and pharmaceutical chemicals. The unsaturated linkage serves as a reactive site for processes of polymerization or alternatively is epoxidized to form useful epoxy resin precursors. The pyrrolines are reacted with inorganic acids to form useful quaternary ammonium salts and when the nitrogen substituent is hydrogen, reaction with carboxylic acids produces useful amides. The pyrrole portion of the product mixture has similar utility, and in addition is re duced by conventional methods to the pyrroline and either may be reduced to the corresponding pyrrolidine. The pyrroline products are dehydrogenated to corresponding pyrroles by treatment with a dehydrogenation catalyst, either in a subsequent operation, or, in a novel further modification of the present process, by inclusion of the catalyst within the reactor where the pyrroline is produced.

To further illustrate the process of the invention, the following examples are provided. It should be understood that the details thereof are not to be regarded as limitations, as they may be varied as will be understood by one skilled in this art.

Example I The vapor-phase reactor employed in this and subsequent examples was a vertically-mounted stainless steel tube having an internal diameter of 0.75 inch and a length of about two feet. The reactor was equipped with a coaxial thermocouple well and a thermoelectric-controlled heating furnace and was packed with glass helices.

To the reactor maintained at 375 C., over a 5-6 hour period, was introduced 10 g. of ethylenimine, 15 cc. of pentane and acetylene (10-15 mole equivalents based on the ethylenimine) together with nitrogen as a carrier gas. The total gas flow rate was 35 cc./min.

The effiuent from the reactor was condensed in ice and Dry Ice traps. After removal of the pentane and approximately 2 g. of unreacted aziridine by fractional distillation, the product, 9 g., was found to be 52% A pyrroline and 48% pyrrole. The total yield of product was 56% based upon the aziridine charged. Product identification was made by mass spectrographic analysis, by the nuclear magnetic resonance and infrared spectra and by comparative gas-liquid chromatographic analysis.

Example ll Under reaction conditions similar to those of Example I, 10 g. of N-methylethylenimine were introduced in the vapor phase, to the reactor together with 10-15 mole equivalents of propyne and nitrogen as a carrier gas. The product mixture, 8.5 g. after removal of the excess propyne and 1.8 g. of unreacted aziridine, was a mixture of 73% l-methyl-h -pyrroline and 27% N-methylpyrrole. The total yield of product was 59% based on the N- methylethylenimine charged.

Example III The procedure of Example I was repeated employing an equivalent amount of propyne in place of the acetylene. After removal of pentane and approximately 1.5

' g. of unreacted aziridine, 9 g. of product was obtained which was found to contain 68% 3-methyl-A -pyrroline and 32% Z-methylpyrrole. Product identification was made by means of mass spectrographic analysis and the nuclear magnetic resonance spectrum.

Example IV Under reaction conditions similar to those of Example I, a mixture of 10 g. of N-methylethylenimine and 42 g. (3 mole equivalents) of hexyne-l was introduced to the reactor employing nitrogen as a carrier gas. After removal of excess hexyne-l and 3.2 g. of unreacted aziridine, 10 g. of product was obtained which was substan tially entirely 1-methyl-3-butyl-A -pyrroline, 13.1. C. at 20 mm. The yield based on the aziridine charged was 42%. Product identification was made by mass spectrographic analysis and the nuclear magnetic resonance spectrum was consistent with the above formula.

Example V When the procedure of Example IV is repeated employing butyne-2 and N-phenylethylenimine as reactants, a good yield of 1-phenyl-2,3-dimethyl-A -pyrroline is obtained.

Example VI A reactor similar to that described in Example I Was prepared containing, as packing, equal amounts of glass helices and 10% Pd-on-carbon, the latter serving as a solid metal dehydrogenation catalyst. A mixture of 10 g. of N-methylethylenimine, 10-15 mole equivalents of acetylene and a 10:1 mixture of nitrogen and hydrogen was introduced to this reactor at a constant rate. The reactor was maintained at 375 C. The product mixture, 8.2 g. after removal of approximately 1.2 g. unreacted aziridine, was found to consist of 25% 1-methyl-A -pyrroline and N-methylpyrrole. Product identification was made by mass spectrographic analysis, by the nuclear magnetic resonance and infrared spectra, and by comparative gas-liquid chromatography.

wherein R and R independently are hydrogen, alkyl, ar-

alkyl, phenyl or alkaryl and a hydrocarbon acetylenic compound of from 2 to carbon atoms of the formula wherein R has the previously stated significance at a temperature from about 250 C. to about 500 C.

2. The process of claim 1 wherein the acetylenic compound is a l-alkyne.

3. The process of producing a A -pyrroline by reacting l-(nonto mono-)alkylaziridine wherein any alkyl substituent has from 1 to 8 carbon atoms with alkyne having from 2 to 10 carbon atoms, in the vapor phase, at a temperature from about 250 C. to about 500 C.

4. The process of producing a A -pyrroline by reacting l-(nonto mono-)alkylaziridine wherein any alkyl substituent has from 1 to 4 carbon atoms with acetylene, in the vapor phase at a temperature from about 300 C. to about 450 C.

5. The process of claim 4 wherein the aziridine is 1- methylaziridine.

6. The process of claim 4 wherein the aziridine is ethylenimine.

7. The process of producing a pyrroline and substantially immediately converting the pyrroline to the corresponding pyrrole by reacting a hydrocarbon aziridine of from 2 to 10 carbon atoms of the formula wherein R and R independently are hydrogen, alkyl, aralkyl, .phenyl or alkaryl and a hydrocarbon acetylenic compound of from 2 to 10 carbon atoms of the formula wherein R has the previously stated significance at a temperature from about 250 C. to about 500 C. in the presence of a solid metal dehydrogenation catalyst.

No references cited.

HENRY R. JILES, Acting Primary Examiner.

MARY E. OBRIEN, Assistant Examiner. 

1. THE PROCESS OF PRODUCING A $3-PYRROLINE BY REACTING A HYDROCARBON AZIRIDINE OF FROM 2 TO 10 CARBON ATOMS OF THE FORMULA 